This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. Primary support for the subproject and the subproject's principal investigator may have been provided by other sources, including other NIH sources. The Total Cost listed for the subproject likely represents the estimated amount of Center infrastructure utilized by the subproject, not direct funding provided by the NCRR grant to the subproject or subproject staff. A key problem in biology is assigning function to proteins of known sequence, sometimes even known structures, but unknown activity. Examples include efforts to de-orphan receptors, determine targets in cell-based (functional) screens, and structural genomics. Much effort has been focused on bioinformatics tools, but a possible role for chemical information has largely been ignored. Many proteins recognize characteristic sets of organic molecules (ligands), either in their normal function or as reagents that interrupt this function. We propose to "fingerprint" proteins using their ligands. Based on the similarity of this fingerprint to those of other proteins, it should be possible to create ligand chemistry-based linkage maps and to infer protein function.